The Mold Fleming Found and the Oxford Team That Turned It Into Medicine

Two stories run through penicillin, and only one of them is the one most people know. In the first, a Scottish bacteriologist comes back from holiday, glances into a sink of dirty glass, and sees a mold killing bacteria. In the second, a refugee chemist, an Australian pathologist, and a quiet tinkerer spend years and a war turning that observation into a medicine that could actually save a human life. The first story made a name. The second made the drug. They are eleven years apart, and the gap between them is where almost everything that mattered happened.

The man who found it

Alexander Fleming came back from a summer holiday in September 1928 to a sink full of dirty glass. He was Professor of Bacteriology at St. Mary’s Hospital in London, and like most bacteriologists he ran a messy bench: stacks of culture plates seeded with staphylococcus, the bacterium behind boils and abscesses and a great deal of death. He had left a pile of them out before going away. Sorting through the discards on September 3, he noticed one plate had been colonized by a blue-green mold, and that something strange had happened around it.

In a clear halo surrounding the mold, the staphylococcus colonies had dissolved. Farther out, where the mold’s influence ran thin, they grew normally. Whatever the mold was making, it was killing the bacteria.

Fleming had a habit of noticing things. A few years earlier he had found that a substance in his own nasal mucus could dissolve certain bacteria — he named it lysozyme — and had never managed to make it into anything useful. The mold was the same kind of puzzle. He grew it, identified it as a Penicillium species, and called the antibacterial juice it secreted “penicillin.” He showed it could hold off dangerous bacteria while leaving white blood cells unharmed, which was the whole problem with the antiseptics of the day: they killed the patient’s tissue along with the germ.

Then he ran into a wall. Penicillin in its raw broth was unstable and present in tiny amounts, and Fleming was a doctor, not a chemist. He could not concentrate it or keep it from falling apart. In February 1929 he presented the work to a London medical society, and when he finished, not a single person asked a question. He published it that June in the British Journal of Experimental Pathology, to about as much notice. A few chemists elsewhere took a run at purifying the stuff and gave up. Fleming kept a culture going and handed samples to anyone who asked, but he stopped treating it as a drug. For most of the 1930s, penicillin was a curiosity in a journal nobody had reread.

The team that read it again

The man who reread it was Ernst Chain, a Jewish biochemist who had fled Berlin in 1933 and, by way of Cambridge, joined the Sir William Dunn School of Pathology at Oxford in 1935. In 1938 he and the school’s head, the Australian pathologist Howard Florey, decided to study the antibacterial substances that some microbes produce against others. Combing the literature, Chain came across Fleming’s nine-year-old paper. Where others had seen a dead end, he and Florey saw an unsolved chemistry problem worth attacking.

They were not romantics about it. The Dunn School in 1939 was a serious laboratory with a chemist’s instincts and, eventually, a wartime urgency. Chain and his colleague Edward Abraham worked out how to coax penicillin out of its broth and concentrate it, controlling temperature and acidity and drying it down by freezing. A young biochemist on the team, Norman Heatley, found the trick that made the process work in quantity: pull the penicillin out of the broth into a solvent, then change the acidity to pull it back into water, shedding a load of impurities at each pass. None of these methods had existed when Fleming threw up his hands.

The decisive experiment was Florey’s idea, and it was the one Fleming had never done: test it in living animals. On May 25, 1940, the team injected eight mice with a lethal dose of Streptococcus. Four were left alone; four were given penicillin. By the next morning the four untreated mice were dead. The four that got the drug were alive. Florey, not a man given to drama, reportedly called the result a miracle. The team published in The Lancet that August.

Bedpans, and a man named Albert Alexander

A mouse needs a pinch of penicillin. A grown human needs vastly more, and there was no factory — there was a few rooms at Oxford. The job of making the drug in bulk fell to Heatley, quiet and endlessly ingenious, and he turned the Dunn School into a mold farm. He grew Penicillium in whatever held liquid and offered a wide surface: cans of sheep dip, pie dishes, biscuit tins, hospital bedpans. When those weren’t enough he designed a flat, stackable ceramic vessel and had 700 of them made by a Staffordshire pottery firm. Six young women, the “penicillin girls,” tended the cultures, and Heatley built a semi-automatic contraption that ran his extraction method continuously, pulling the drug out as the mold made it. The first big ceramic batch was seeded on Christmas Day, 1940.

By early 1941 they had enough to try on a person. The patient was Albert Alexander, a 43-year-old Berkshire constable brought to the Radcliffe Infirmary in Oxford with a savage infection spreading across his face, into his scalp and an eye, that ordinary treatment could not stop. The story long told was that he had scratched himself on a rose thorn while gardening; later research, supported by his own family, holds that the wound came from shrapnel in a German air raid in late 1940, the truth softened into roses for wartime morale. Either way, he was dying of blood poisoning.

On February 12, 1941, he was given penicillin by injection. Within a day his fever fell, his appetite returned, the infection began to retreat. Crude mold filtrate had cleared up eye infections a decade earlier, in drops; this was the first proof that the drug could go into a human bloodstream and beat back an infection that had spread through the whole body.

And then they ran out. There was so little penicillin that the team filtered it back out of Alexander’s own urine and re-injected it to stretch the supply. It wasn’t enough. The salvaged doses couldn’t keep pace with the infection, it surged back, and on March 15 Albert Alexander died.

His death was not a defeat, and the team knew it. He had shown them the thing they most needed to know: that penicillin could pull a human being back from the edge of a fatal infection. What killed him was supply, not the drug. The lesson was that the medicine existed and the manufacturing did not.

Two names, one prize

That summer, with Britain at war and short of everything, Florey and Heatley flew to the United States carrying samples of the mold to find someone who could make penicillin by the ton. American labs and companies, soon spurred by the war, scaled fermentation from bedpans to industrial vats in time for the drug to reach Allied troops by the 1944 invasions, where it saved limbs and lives that infection would otherwise have taken.

Fleming, Florey, and Chain shared the Nobel Prize in 1945. Fleming, by then famous as the lone genius who discovered penicillin, used his Nobel lecture to warn that bacteria could learn to resist the drug if it were misused — a caution the world would spend the next eighty years proving correct. The discovery had been an accident on a dirty plate. The medicine took a refugee, a pathologist, a man growing mold in bedpans, and one policeman who lived just long enough to show it could work.